Obesity-induced adipocytes promote diabetes mellitus by regulating β islet cell function through exosome miR-138-5p
Abstract Insulin dysfunction can lead to type 1 diabetes mellitus (T1DM), inducing an increase in blood glucose levels. Unfortunately, there remains a need for more effective clinical treatments for DM. Obesity is closely associated with islet dysfunction, but these inside mechanisms remain unclear....
Saved in:
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-05-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-01564-4 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract Insulin dysfunction can lead to type 1 diabetes mellitus (T1DM), inducing an increase in blood glucose levels. Unfortunately, there remains a need for more effective clinical treatments for DM. Obesity is closely associated with islet dysfunction, but these inside mechanisms remain unclear. We indicated that obesity-induced adipocytes inhibit insulin secretion (IS) from β islet cells (β-cells) by elevating the expression of their exosome miR-138-5p. Our study proved the high expression of miR-138-5p in exosomes isolated from the fat tissue of obese mice, as well as in exosomes derived from obesity-induced 3T3-L1 cells. The underlying mechanism possibly involves the upregulation of miR-138-5p which suppressed IS while increasing apoptosis in MIN6 cells. miR-138-5p knockdown upregulated insulin production and decreased apoptosis in MIN6 cells. Moreover, dual-luciferase reporter assays revealed the direct regulating effects of miR-138-5p on SOX4. Moreover, SOX4 expression affects the abundance of proteins involved in the Wnt/β-catenin pathway. Under obesity conditions, miR-138-5p in adipocyte exosomes affects IS and ultimately β-cell function by regulating the SOX4-mediated Wnt/β-catenin pathway in β cells. These results not only presented new insights into the interaction between obesity and T1DM but also provide new possible therapeutic mechanisms for obesity-related T1DM. |
|---|---|
| ISSN: | 2045-2322 |